In September 1928 Alexander Fleming returned to his cramped laboratory at St Mary's Hospital in London after a summer break and began sorting through a stack of glass dishes he had left piled by the bench. Fleming was a brilliant but famously untidy worker, and one of the culture plates of Staphylococcus bacteria had been contaminated by a stray mould. Where the fuzzy blue-green growth had taken hold, the surrounding colonies of bacteria had dissolved into clear rings, as though something seeping out of the mould had killed them. "That's funny," he is supposed to have remarked — one of the most quoted understatements in science.
The mould was a strain of Penicillium, and Fleming named the substance it produced penicillin. He published his findings in 1929, showed the "mould juice" could kill many dangerous bacteria without harming animal tissue, and then largely moved on. Fleming was a bacteriologist, not a chemist, and he could not purify the compound or produce it in any useful quantity. Penicillin was unstable, hard to extract, and for over a decade it languished as a laboratory curiosity — a fact that makes the popular telling of a lone genius saving the world thoroughly misleading.
The Oxford team
The real transformation of penicillin from curiosity into medicine happened at the University of Oxford at the end of the 1930s, led by the Australian pathologist Howard Florey and the German-born biochemist Ernst Chain, a refugee from Nazi Germany. With a small team — the biochemist Norman Heatley devised much of the ingenious apparatus for growing and extracting the mould — they set about doing the hard chemistry Fleming never could. On 25 May 1940 they ran the decisive experiment: eight mice were infected with a lethal dose of streptococci, four were given penicillin, and by the next morning the treated mice were alive while the untreated ones were dead.
Human trials followed in 1941. The first patient, an Oxford policeman named Albert Alexander, had a raging infection said to have begun with a scratch from a rose bush. Penicillin produced a dramatic improvement, but the team's supply was so scarce that they recycled the drug from the patient's own urine — and still ran out. Alexander relapsed and died. The lesson was brutally clear: the science worked, but without industrial-scale production penicillin could save almost no one.
Bread mould and mass production
With wartime Britain unable to spare the resources, Florey and Heatley flew to the United States in 1941 to enlist American industry. Researchers at a government laboratory in Peoria, Illinois, made two key breakthroughs: they grew the mould in corn steep liquor, a cheap by-product that dramatically boosted yields, and they hunted for more productive strains. The winner came from a mouldy cantaloupe melon found in a Peoria market, whose Penicillium produced far more penicillin than Fleming's original. By the D-Day landings of June 1944, penicillin was being manufactured in enormous quantities and was saving thousands of Allied soldiers from wound infections that would once have been fatal.
In 1945 the Nobel Prize in Physiology or Medicine was shared by Fleming, Florey and Chain — a division that quietly acknowledged the discovery was not one man's work. Fleming, by then a celebrity, used his own Nobel lecture to issue a warning that has aged remarkably well: that careless use of penicillin would breed resistant bacteria. He described how easy it was, in the laboratory, to make microbes resistant by exposing them to doses too small to kill them, and cautioned that the same could happen in the body. The antibiotic era he helped open would, within decades, be shadowed by exactly the problem he foresaw.
The story is often told as a lucky accident, and the contamination genuinely was one. But Louis Pasteur's line that fortune favours the prepared mind fits neatly: many scientists had noticed moulds killing bacteria, and Fleming himself had earlier discovered lysozyme, a natural antibacterial substance in tears and saliva. What turned a chance observation into a medicine that has since saved an incalculable number of lives was not the accident but the decade of unglamorous chemistry that followed it. It is worth remembering, too, that penicillin was not the first antibacterial breakthrough of the era: the German scientist Gerhard Domagk had already shown in the 1930s that a red dye called Prontosil could treat streptococcal infections, launching the sulfa drugs. Penicillin's advantage was that it killed a far wider range of bacteria and was, in proper doses, remarkably safe. The mould in Fleming's dish, in other words, arrived at exactly the moment medicine was primed to understand what it was looking at.
Quiz nuggets
- Alexander Fleming noticed penicillin's effect in 1928 at St Mary's Hospital, London, after a Penicillium mould contaminated a Staphylococcus plate.
- Penicillin was turned into a usable drug in the late 1930s by an Oxford team led by Howard Florey and Ernst Chain, with Norman Heatley designing the extraction methods.
- The first patient treated, in 1941, was an Oxford policeman named Albert Alexander, who relapsed and died when the scarce supply ran out.
- Mass production was cracked in the United States using corn steep liquor and a high-yielding mould found on a cantaloupe melon in Peoria, Illinois.
- Fleming, Florey and Chain shared the 1945 Nobel Prize in Physiology or Medicine, and Fleming used his lecture to warn about antibiotic resistance.